• Journal of Ginseng Research
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• 제19권1호
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• pp.45-50
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• 1995

(20S)- and (20R)-protopanaxadiol were prepared from crude ginseng saponin by chemical treatment. The $^{1}H$- and $^{13}C$-NMR signals of these compounds were fully assigned by various NMR techniques such as DEPT, 1H-1H COSY, HMQC, HMBC and NOESY.

• 약학회지
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• 제35권5호
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• pp.432-437
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• 1991

A mixture of 20(R)- and 20(S)-ginsenoside Rg$_{3}$ was obtained under mild acidic hydrolysis from protopanaxadiol saponins, ginsenosides Rb$_{1}$, Rb$_{2}$, Rc and Rd. The product was acetylated to give the peracetates, which were further converted into 20(R)-ginsenoside Rg$_{3}$, 20(S)-ginsenoside Rg$_{3}$, 20(R)-ginsenoside Rh$_{2}$ and 20(S)-ginsenoside Rh$_{2}$ by the direct alkaline treatment depending upon two kinds of temperature conditions respectively. The structure and physicochemical properties of a prosapogenin, 20(R)-ginsenoside Rh$_{2}$, were investigated.

• Journal of Pharmaceutical Investigation
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• 제34권5호
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• pp.385-391
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• 2004

The purpose of the present study was to formulate the aqueous solution of $20-O-{\beta}-D-glucopyranosyl-20(S)-protopanaxadiol\;(IH-901)$, an intestinal bacterial metabolic derivative from Ginseng protopanaxadiol saponin. For this purpose, the effects of various solubilization agents such as cosolvents [ethanol, propylene glycol (PG), polyethylene glycol 300 (PEG 300), polyethylene glycol 400 (PEG 400), glycerin], surfactants $(Tween\;80,\;Cremophor^{\circledR}\;RH40,\;Cremophor^{\circledR}\;EL,\;Poloxamer\;407,\;Poloxamer\;188)$ and a complexation agent $[hydroxypropyl-{\beta}-cyclodextrin\;(HPBCD)]$, on the solubility of IH-90l in aqueous solution were evaluated. The solubility of IH-901 in water was under $1\;{\mu}g/ml\;at\;20^{\circ}C$. Cosolvents such as ethanol, PG, PEG 300, PEG 400 and glycerin did not enhance the solubility of IH-901 at the 0 - 40% concentration range. The solubility of IH-901 was significantly elevated by the addition of cosolvents over the 80% concentration range. On the other hand, tween 80, $Cremophor^{\circledR}\;EL,\;Cremophor^{\circledR}\;RH40$ and HPBCD showed enhanced effects on the solubility of IH-901. The enhanced effects of Poloxamer 407 or Poloxamer 188 on the IH-901 solubility were less pronounced compared with $Cremophor^{\circledR}\;EL\;or\;Cremophor^{\circledR}\;RH40$. As a results, $Cremophor^{\circledR}$ aqueous solution was selected as an optimum solvent system. The aqueous solutions containing 10% $Cremophor^{\circledR}\;EL$ and 7% $Cremophor^{\circledR}\;RH40$ were formulated as dosing solutions containing 5.0 mg/ml of IH-901 for its intravenous and oral administration, respectively. The formular showed physical stability after stored for 7 days at $4^{\circ}C$.

• Journal of Ginseng Research
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• 제44권5호
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• pp.690-696
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• 2020

Background: As the main metabolites of ginsenosides, 20(S, R)-protopanaxadiol [PPD(S, R)] and 20(S, R)-protopanaxatriol [PPT(S, R)] are the structural basis response to a series of pharmacological effects of their parent components. Although the estrogenicity of several ginsenosides has been confirmed, however, the underlying mechanisms of their estrogenic effects are still largely unclear. In this work, PPD(S, R) and PPT(S, R) were assessed for their ability to bind and activate human estrogen receptor α (hERα) by a combination of in vitro and in silico analysis. Methods: The recombinant hERα ligand-binding domain (hERα-LBD) was expressed in E. coli strain. The direct binding interactions of ginsenosides with hERα-LBD and their ERα agonistic potency were investigated by fluorescence polarization and reporter gene assays, respectively. Then, molecular dynamics simulations were carried out to simulate the binding modes between ginsenosides and hERα-LBD to reveal the structural basis for their agonist activities toward receptor. Results: Fluorescence polarization assay revealed that PPD(S, R) and PPT(S, R) could bind to hERα-LBD with moderate affinities. In the dual luciferase reporter assay using transiently transfected MCF-7 cells, PPD(S, R) and PPT(S, R) acted as agonists of hERα. Molecular docking results showed that these ginsenosides adopted an agonist conformation in the flexible hydrophobic ligand-binding pocket. The stereostructure of C-20 hydroxyl group and the presence of C-6 hydroxyl group exerted significant influence on the hydrogen bond network and steric hindrance, respectively. Conclusion: This work may provide insight into the chemical and pharmacological screening of novel therapeutic agents from ginsenosides.

• Journal of Ginseng Research
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• 제42권4호
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• pp.512-523
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• 2018

Background: 20(S)-Protopanaxadiol (20S-PPD) is a fully deglycosylated ginsenoside metabolite and has potent dermal antiaging activity. However, because of its low aqueous solubility and large molecular size, a suitable formulation strategy is required to improve its solubility and skin permeability, thereby enhancing its skin deposition. Thus, we optimized microemulsion (ME)-based hydrogel (MEH) formulations for the topical delivery of 20S-PPD. Methods: MEs and MEHs were formulated and evaluated for their particle size distribution, morphology, drug loading capacity, and stability. Then, the deposition profiles of the selected 20S-PPD-loaded MEH formulation were studied using a hairless mouse skin model and Strat-M membrane as an artificial skin model. Results: A Carbopol-based MEH system of 20S-PPD was successfully prepared with a mean droplet size of 110 nm and narrow size distribution. The formulation was stable for 56 d, and its viscosity was high enough for its topical application. It significantly enhanced the in vitro and in vivo skin deposition of 20S-PPD with no influence on its systemic absorption in hairless mice. Notably, it was found that the Strat-M membrane provided skin deposition data well correlated to those obtained from the in vitro and in vivo mouse skin studies on 20S-PPD (correlation coefficient $r^2=0.929-0.947$). Conclusion: The MEH formulation developed in this study could serve as an effective topical delivery system for poorly soluble ginsenosides and their deglycosylated metabolites, including 20S-PPD.

• Journal of Ginseng Research
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• 제43권1호
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• pp.116-124
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• 2019

Background: Ginsenosides are known as the principal pharmacological active constituents in Panax medicinal plants such as Asian ginseng, American ginseng, and Notoginseng. Some ginsenosides, especially the 20(R) isomers, are found in trace amounts in natural sources and are difficult to chemically synthesize. The present study provides an approach to produce such trace ginsenosides applying biotransformation through Escherichia coli modified with relevant genes. Methods: Seven uridine diphosphate glycosyltransferase (UGT) genes originating from Panax notoginseng, Medicago sativa, and Bacillus subtilis were synthesized or cloned and constructed into pETM6, an ePathBrick vector, which were then introduced into E. coli BL21star (DE3) separately. 20(R)-Protopanaxadiol (PPD), 20(R)-protopanaxatriol (PPT), and 20(R)-type ginsenosides were used as substrates for biotransformation with recombinant E. coli modified with those UGT genes. Results: E. coli engineered with $GT95^{syn}$ selectively transfers a glucose moiety to the C20 hydroxyl of 20(R)-PPD and 20(R)-PPT to produce 20(R)-CK and 20(R)-F1, respectively. GTK1- and GTC1-modified E. coli glycosylated the C3-OH of 20(R)-PPD to form 20(R)-Rh2. Moreover, E. coli containing $p2GT95^{syn}K1$, a recreated two-step glycosylation pathway via the ePathBrich, implemented the successive glycosylation at C20-OH and C3-OH of 20(R)-PPD and yielded 20(R)-F2 in the biotransformation broth. Conclusion: This study demonstrates that rare 20(R)-ginsenosides can be produced through E. coli engineered with UTG genes.

• Journal of Dairy Science and Biotechnology
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• 제32권1호
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• pp.47-53
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• 2014

본 연구는 김치에서 분리한 L. acidophilus를 이용하여 홍삼 농축액의 진세노사이드 변화 및 폴리페놀 변화량을 확인하였고, 발효유제품 중 신선치즈를 선정하여 홍삼 발효물의 기능성 소재로의 사용 가능성을 확인하였다. 홍삼농축액3% 처리구에 L. acidophilus 유산균주를 $1.0{\times}10^8CFU/mL$로 첨가하여 $40^{\circ}C$에서 24시간 발효한 경우 유산균수는 발효 0시간째 $3.5{\times}10^8CFU/mL$에서 발효 16시간째 $3.8{\times}10^8CFU/mL$로 증가하였다가 그 후 감소하여 발효 24시간째에는 $2.2{\times}10^8CFU/mL$로 측정되었다. Ginsenoside 전환 양상은 고분자 물질로는 Rb1, Rb2, Rc, Rd, Re, Rf, Rg1이 검출되었고, 저분자 물질로는 Rg3(20S), Rg3(20R), Rh2(20S), Rh1(20R), Rh2(20S), Rh2(20R), F1, Compound K, Protopanaxadiol(20S), Protopanaxadiol(20R)이 검출되었다. 고분자 물질이 감소함에 따라 저분자 물질인 Rg3(20S) 및 Rg3(20R), protopanaxadiol(20R), F1, Compound K 등이 증가하였다. 홍삼 발효물의 총 페놀 화합물의 변화량은 에틸아세테이트 분획물 및 16% ACN 분획물에서 발효시간이 증가할수록 폴리페놀 함량이 증가하였다. 홍삼 발효물을 첨가하여 제조한 신선치즈의 저장 중 품질변화를 분석하였으며, 홍삼 발효물의 첨가농도가 높아질수록 pH는 저장기간 동안 감소하였고, 산도 및 유산균수는 증가하였다. 관능검사 결과 홍삼 발효물 1% 처리구가 대조구와 유사한 평가를 얻었으며, 이때의 사포닌 함량은 14.8 mg%, 총 페놀함량은 3.7 mg%이었다. 따라서 향후 동물모델을 통한 추가적인 효능검증이 이뤄진다면 홍삼 발효물을 이용한 기능성 강화 고부가가치 신선치즈 제조가 가능할 것으로 보인다.

• Journal of Ginseng Research
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• 제38권3호
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• pp.194-202
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• 2014

Background: Ginsenosides, the major ingredients of Panax ginseng, have been studied for many decades in Asian countries as a result of their wide range of pharmacological properties. The less polar ginsenosides, with one or two sugar residues, are not present in nature and are produced during manufacturing processes by methods such as heating, steaming, acid hydrolysis, and enzyme reactions. $^1H$-NMR and $^{13}C$-NMR spectroscopic data for the identification of the less polar ginsenosides are often unavailable or incomplete. Methods: We isolated 21 compounds, including 10 pairs of 20(S) and 20(R) less polar ginsenosides (1-20), and an oleanane-type triterpene (21) from a processed ginseng preparation and obtained complete $^1H$-NMR and $^{13}C$-NMR spectroscopic data for the following compounds, referred to as compounds 1-21 for rapid identification: 20(S)-ginsenosides Rh2 (1), 20(R)-Rh2 (2), 20(S)-Rg3 (3), 20(R)-Rg3 (4), 6'-O-acetyl-20(S)-Rh2 [20(S)-AcetylRh2] (5), 20(R)-AcetylRh2 (6), 25-hydroxy-20(S)-Rh2 (7), 25-hydroxy-20(S)-Rh2 (8), 20(S)-Rh1 (9), 20(R)-Rh1 (10), 20(S)-Rg2 (11), 20(R)-Rg2 (12), 25-hydroxy-20(S)-Rh1 (13), 25-hydroxy-20(R)-Rh1 (14), 20(S)-AcetylRg2 (15), 20(R)-AcetylRg2 (16), Rh4 (17), Rg5 (18), Rk1 (19), 25-hydroxy-Rh4 (20), and oleanolic acid 28-O-b-D-glucopyranoside (21).

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 2002년도 학술대회지
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• pp.253-261
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• 2002

To follow the metabolic fate of aglycone of ginseng saponins,in vitro and in vivo experiments were performed. Incubation of 20(S)-prtopanaxatriol (1) with rat liver S9 fraction afforded unique ocotillol derivatives, 20, 24-epoxysides (3 and 4). Also 20(S)-prtopanaxadiol (2) gave the corresponding epoxides (5). Healthy volunteers were taken with Sanchi Ginseng, which contains protopanaxatriol and protopanaxadiol saponins and no ocotillol saponins. From the alkaline hydrolysate of the urine samples of these volunteers,3 was detected as well as 1, and the ratio of 3/1 increased up to 2.0 at the maximum at 50 hrs. Biochemical significance of the ocotillol derivatives is discussed, since the main bioactive saponin in Panax vietnamensis is an ocotillol-type saponin, majonoside R2 (7).

• 대한화장품학회:학술대회논문집
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• 대한화장품학회 2003년도 IFSCC Conference Proceeding Book I
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• pp.741-762
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• 2003

Ginsenosides, the major active ingredients of ginseng, show a variety of biomedical efficacies such as anti-aging, anti oxidation and anti-inflammatory activities. To understand the effects of compound K (20-O-D-glucopyranosyl-20 (S)-protopanaxadiol), one of the major metabolite of ginsenosides on the skin, we assessed the expression level of ∼ 100 transcripts in compound K-treated HaCaT cells using cDNA microarray analysis. Compound K treatment induced differential expression of 21 genes, which have been reported to be involved in the organization of ECM structure as well as defense responses in human skin cells. One of the most interesting findings is 2-fold increase in hyaluronan synthase2 (HAS2) gene expression by compound K. We found that change in expression of HAS2 gene represents a specific response of HaCaT cells to compound K because hyaluronan synthase 1, 3 was not changed by treatment with compound K. We also demonstrated that the compound K effectively induced hyaluronan synthesis in human skin cells and hairless mouse skin. The human clinical study indicates that topical application of compound K-containing oil-in-water emulsion showed improvement of xerosis, wrinkle and fine lines in the aged skin. We concluded that compound K has anti-aging effects by the induction of HAS2 gene expression and following hyaluronan synthase.